Production of high purity radioactive isotopes



United States Patent 3,382,152 PRODUCTION OF HIGH PURITY RADIOACTIVEISOTOPES Ephraim Lieberman, Suifern, N.Y., and Wayne J. Gemmill,Milford, Pa., assignors to Union Carbide Corporation, a corporation ofNew York No Drawing. Filed Sept. 28, 1964, Ser. No. 399,842

' 18 Claims. (Cl. 176-16) This invention relates to the production ofhigh .purity radioactive isotopes, particularly molybdenum-99 andtechnetium-99m. Technetttium-99m, which has a half-life of six hours, isproduced by the spontaneous radioactive beta decay of molybdenum-99. Thelatter has a half-life of 67 hours.

High purity Tc is used primarily as a radioisotope in medical researchand diagnosis. It is well suited for liver and brain scanning, and ispreferred over other radioactive isotopes because of its short half-lifewhich results in reduced exposure of the organs to radiation.

Since the radioisotope sought to be used has such a short half-life, itis common practice to ship the users of the isotope the parent element;in this case M0 The user then extracts the Tc from the Mo as his needsrequire.

In the past, radioactive molybdenum-99 has been recovered as a fissionproduct formed by the fissioning of uranium-235 in a nuclear reactor.This method of producing M0 has several important shortcomings. One isthat the M0 has to be separated from the numerous other radioactivefission products of U-235 such as strontium-90, yttrium-91,zirconium-95, niobium-95, ruthenium-103, ruthenium-106, iodine-131,cerium-141, cesium-137, cerium-144, prometh-ium-l47 and many others.Some of these fission products are long lived, and due to theirradioactivity are difficult to handle without elaborate shielding.

As a result of separation problems, pure molybdenum-99 and consequentlypure Tc cannot be obtained from U-235 fissioning because traces offission products such as iodine-131 and ruthenium-103 frequently remainin the separated product. In addition, this technique presentsradioactive waste disposal problems.

It is an object of this invention to provide a more efficient method ofproducing radioactive molybdenum from which radioactive technetium maybe extracted. It is another object of this invention to produceradioactive molybdenum by a method which avoids the need for separatingradioactive fission products and avoids problems relating to disposingof radioactive waste resulting from the fissioning of U-235. It isanother object of this invention to prepare high purity technetium-99which contains no traces of fission products.

It has now been discovered that the aforementioned objects can beachieved by a process which comprises irradiating a molybdenumcontaining material in the presence of a neutron flux until the desiredamount of Mo activity is formed, dissolving the irradiated material(containing M0 in a base, adjusting the pH of the solution to be acidicand above pH 2.5, contacting an inorganic anion exchange material withthe pH adjusted solution (thereby loading the molybdenum on the anionexchange material) and then selectively eluting or extractingtechnetium-99m, formed by the radioactive decay of molybdenum-99, fromthe loaded anion exchange material with an acid.

The present method offers several advantages over prior art methods ofpreparing technetium-99m. One of these is elimination of the need toseparate radioactive molybdenum from other radioactive fission products.Another is a considerable reduction in the radioactive waste disposalproblem. A still further advantage of this invention is that a productof high purity is obtained containing no traces of other radioactivefission products. The purity of T0 is of considerable importance becauseof its medicinal use.

In order to more fully understand the invention, the following example,which is the preferred embodiment of the invention, is given by way ofillustration only and is not intended to limit the scope of thisinvention.

EXAMPLE 0.38 gram of M00 were placed in a inch aluminum capsule andsealed. The capsule was irradiated for hours in a neutron flux of 5 x10n/cm. -sec. The resulting material containing radioactive M0 had anactivity of about 135 m-ilicuries. Folio-wing irradiation the M00 wasdissolved in approximately 10 ml. of 40 percent NH,OH. The solution ofammonium molybdate was first neutralized to a pH of 7 with 6 M HNO andthen acidified to a pH of 3.0 to 3.5 with 1 M HNO Prior to loading theabove radioactive solution on an alumina anion-exchange column, thecolumn containing 6 grams of 100 to 200 mesh alumina was washed withwater and 0.1 M HNO Effluent from th washing step was acidic (pH 2-6)before the column was loaded. The solution of ammonium molybdate afterhaving its pH adjusted to 3.0 to 3.5 (and which contains M0 was loadedon the alumina column at a flow rate of about l-2 ml. per min. After thecolumn was loaded, it was Washed with about 150 ml. of 0.1 M HCl inorder to remove the small quantities of M0 that would subsequently washthrough during Tc elution and contaminate the product solution.

The loaded column which contained about milicuries of activity cansubsequently be eluted or milked repeatedly for Tc as it is formed with25 ml. portions of 0.1 M HCl solution. This is done by passing thedesired volume of 0.1 M HCl through the column and collecting theefiluent.

Numerous variations of the preferred embodiment described above may bepracticed, as will be apparent to those skilled in the art, withoutdeparting from the basic concepts of the present invention. Thus, whileM00 is the preferred target material for the production of M0 othermolybdenum containing materials may be used. Such materials include, forexample, molybdenum sesquioxide, M0 0 molybdenum dioxide, M00 molybdenumpentoxide, M0 0 hydrated molybdenum oxide (moly blue), Mo -xH O;molybdic acid H MoO and mixtures thereof.

Separation of Tc from Mo can be efifected by contacting the M0 (in theform of molybdate ions) with alumina, followed by selective removal ofTc (in the form of the TcO, ion) from the loaded alumina. A column ofalumina is preferably used, however, the separation can be made byslurrying the molybdate ion containing solution with finely dividedalumina in a container (thereby loading the alumina with molybdateions), separating the solids from the liquid, for example, by filtrationand then removing the T0 from the alumina particles by reslurrying thealumina in an acid and then separating the dissolved Tc" from theunloaded alumina solids. Use of a column is, of course, far simpler andmore etficient.

The exact nature of the exchange mechanism by which the molybdenum isloaded on alumina and by which the T0 is eluted is not entirely certain.While not wishing to be limited to any theory, it is believed to be anion exchange mechanism whereby molybdate ions are loaded on theacidified alumina column in exchange for OH ions. Upon elution, the Tois removed from the column as pertechnate, TcO ions in exchange for C1ions. However, the ion exchange reaction appears to be limited to asurface phenomena, and it is therefore possible that the mechanism isactually a surface adsorption phenomena. It is most likely a combinationof both ion exchange and adsorption. Thus, While the material isreferred to in this disclosure as an inorganic anion exchange material,it is to be understood that the materials rather than the mechanismwhether ion exchange or adsorption are intended thereby. Alumina is thepreferred exchange material. Other materials, however, which arechemically stable in the system, stable to the radiation emitted in thesystem, and which are able to exchange the molybendum and technetiumions can be used in place of alumina. Such materials include theinorganic refractory oxides of zirconium, thorium, tungsten and silicon.Suitable illustrative materials include Zirconia (ZrO thoria (ThOtungsten trioxide (W and silica (SiO These materials have an affinityfor anions when their surfaces have been rendered acidic.

Bases other than NH OH may be used to dissolve the irradiated molybdenumcontaining material, provided they will not interfere with subsequentloading and elution of the inorganic anion-exchange material. Suitablebases include, for example, NaOH and KOH. Ammonium hydroxide ispreferred.

Following dissolution of the irradiated molybdenum containing materialit is essential that the solution be acidified and be above pH 2.5 At apH below 2.5 precipitation results, while at an alkaline pH themolybdate ion will not load properly on the exchange material. Thepreferred range is pH 3.0 to 3.5. Adjustment of the pH and washing ofthe exchange material is preferably done with HNO HCl is the preferredacid used for the preferential elution of Tc from the exchange material.ther mineral acids, however, such as HNO may also be used.

The amount of radiation to which the molybdenum containing targetmaterial is subjected is not critical and both the time and intensity ofthe neutron flux may be varied considerably from that shown in thepreferred embodiment. It is merely necessary that the target material beirradiated until the desired amount of Mo activity is formed. Aconvenient amount is about 100-300 millicuries of Mo" per loaded column,or about 200-1000 millicuries per gram of irradiated M00 What is claimedis:

1. A process for producing radioactive technetium-99m which comprisesthe steps of:

(l) irradiating a base-soluble molybdenum containing material in aneutron flux until the desired amount of M0 activity is formed,

(2) dissolving the irradiated molybdenum containing material, containingthe radioactive M0, in a base,

(3) adjusting the pH of the solution prepared in step (2) to be acidicand above pH 2.5,

(4) contacting an inorganic anion exchange material with the pH adjustedsolution of step (3) thereby loading the molybdenum on the exchangematerial, and

(5) extracting technetium-99m, formed by the radioactive decay of M0from the loaded anion exchange material with an acid.

2. The process of claim 1 wherein the inorganic anion exchange materialis alumina.

3. The process of claim 2 wherein the base used to dissolve theirradiated material is ammonium hydroxide.

4. The process of claim 2 wherein the pH of the solution prepared instep (2) is adjusted to be within the range of 3.0 to 3.5.

5. The process of claim 2 wherein the particle size of the alumina is100 to 200 mesh.

6. The process of claim 2 wherein the acid used for extracting thetechnetium-99m from the loaded alumina is hydrochloric acid.

7. A process for producing radioactive technetium-99m which comprisesthe steps of:

(1) irradiating M00 in a neutron flux until the desired amount of M0activity is formed,

(2) dissolving the irradiated M00 containing radioactive Mo in ammoniumhydroxide,

(3) adjusting the pH of the solution formed in step (2) to be acidic andabove pH 2.5,

(4) contacting a column of alumina with the pH adjusted solution of step(3) thereby loading the alumina With molybdate ions, and

(5) eluting technetium-99m, formed by the radioactive decay of M0 fromthe loaded alumina column with hydrochloric acid.

8. The process of claim 7 wherein the pH of the solution formed in step(2) is adjusted to be within the range of 3.0 to 3.5.

9. A process for producing radioactive technetium-99m which comprisesthe steps of:

(1) providing a solution of ammonium molybdate in which at least some ofthe molybdenum is radioactive 99 (2) adjusting the pH of the solution tobe acidic and above pH 2.5,

(3) contacting a column of alumina with the pH adjusted solution of step(2), thereby loading the column with molybdate ions, and

(4) eluting technetium-99m, formed by the radioactive decay of M0 fromthe loaded alumina column with an acid.

10. The process of claim 9 wherein the pH of the solution is adjusted tobe within the range of 3.0 to 3.5.

11. The process of claim 9 wherein the acid used for eluting the loadedalumina column is hydrochloric acid.

12. A process for producing radioactive technetium- 99rn which comprisesthe steps of:

(1) providing a solution containing molybdate ions, which is acidic, hasa pH above 2.5, and in which at least some of the molybdenum isradioactive M0 (2) loading a column of alumina with the solution ofstep 1) and (3) eluting technetium-99m, formed by the radioactive decayof M0 from the loaded alumina column with an acid.

13. The process of claim 12 wherein the pH of the solution is adjustedto be within the range of 3.0 to 3.5.

14. The process of claim 12 wherein the acid used for eluting the loadedalumina column is hydrochloric acid.

15. A process for producing a solution containing radioactivemolybdenum-99, from which solution radioactive molybdenum-99 can beloaded onto an inorganic anion exchange material, which processcomprises the steps of:

(l) irradiating M00 in a neutron flux until the desired amount of Moactivity is formed,

(2) dissolving the irradiated M00 containing radioactive Mo in a base,and

(3) adjusting the pH of the solution formed in step (2) to be acidic andabove pH 2.5.

16. A process for producing a solution containing radioactivemolybdenum-99, from which solution radioactive molybdenum-99 can beloaded onto alumina, which process comprises the steps of:

(l) irradiating M00 in a neutron flux until the desired amount of Moactivity is formed,

(2) dissolving the irradiated M00 containing radioactive M0 in ammoniumhydroxide and,

(3) adjusting the pH of the solution prepared in step (2) to be withinthe range of 3.0 to 3.5.

17. A process for producing the combination comprising alumina havingloaded thereon radioactive molybdenum-99 which process comprises thesteps of:

(1) irradiating M00 in a neutron flux until the desired amount of Moactivity is formed,

(2) dissolving the irradiated M00 containing radioactive M0 in a base,

5 (3) adjusting the pH of the solution formed in step (2) to be acidicand above pH 2.5, and

(4) loading the pH adjusted solution of step (3) on a column of alumina.

18. A process for producing the combination comprising alumina havingloaded thereon radioactive molybdenum-99 which process comprises thesteps of (1) irradiating M00 in a neutron flux until the desired amountof M0 activity is formed,

(2) dissolving the irradiated MoO containing radioactive M0 in ammoniumhydroxide,

(3) adjusting the pH of the solution prepared in step (2) to be withinthe range of 3.0 to 3.5, and

(4) loading the pH adjusted solution of step (3) on a column of alumina.

References Cited O 1 CARL D. QUARF'ORTH, Primary Examiner.

L. DEWAY'NE RUTLEDGE, Examiner.

H. E. BEHREND, Assistant Examiner.

1. A PROCESS FOR PRODUCING RADIOACTIVE TECHNETIUM-99M WHICH COMPRISESTHE STEPS OF: (1) IRRADIATING A BASE-SOLUBLE MOLYBDENUM CONTAININGMATERIAL IN A NEUTRON FLUX UNTIL THE DESIRED AMOUNT OF MO99 ACTIVITY ISFORMED, (2) DISSOLVING THE IRRADIATED MOLYBDENUM CONTAINING MATERIAL,CONTAINING THE RADIOACTIVE MO99, IN A BASE, (3) ADJUSTING THE PH OF THESOLUTION PREPARED IN STEP (2) TO BE ACIDIC AND ABOVE PH 2.5, (4)CONTACTING AN INORGANIC ANION EXCHANGE MATERIAL WITH THE PH ADJUSTEDSOLUTION OF STEP (3) THEREBY LOADING THE MOLYBDENUM ON THE EXCHANGEMATERIAL, AND (5) EXTRACTING TECHNETIUM-99M, FORMED BY THE RADIOACTIVEDECAY OF MO99, FROM THE LOADED ANION EXCHANGE MATERIAL WITH AN ACID.